title: Autoimmune lymphoproliferative syndrome misdiagnosed as hemophagocytic lymphohistiocytosis.
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. Unfortunately, these clinical findings are also noted in other childhood lymphoproliferative conditions, such as leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the recognition that her symptoms and laboratory values were consistent with a somatic FAS mutation leading to ALPS. This case should alert pediatricians to include ALPS in the differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenias; obtain discriminating screening laboratory biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS mutations when germ-line mutation testing is negative.
authors.affiliation: ALPS Unit, LI/NIAID, National Institutes of Health, DHHS, Room 12C106, Building 10, 10 Center Dr, Bethesda, MD 20892-1899. krao@niaid.nih.gov.
authors.forename: Amanda
authors.initials: A
authors.lastname: Rudman Spergel
authors.forename: Kelly
authors.initials: K
authors.lastname: Walkovich
authors.forename: Susan
authors.initials: S
authors.lastname: Price
authors.forename: Julie E
authors.initials: JE
authors.lastname: Niemela
authors.forename: Dowain
authors.initials: D
authors.lastname: Wright
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: V Koneti
authors.initials: VK
authors.lastname: Rao
mesh_terms: D056735:Autoimmune Lymphoproliferative Syndrome / Q000150:complications / Q000175:diagnosis*; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000175:diagnosis*
keywords: ALPS; HLH; apoptosis; cytopenias; lymphadenopathy; splenomegaly